The objectives of this study was to examine and identify the early molecular events that occur during growth and differentiation of pluripotential stem cells into lymphoid lineages. It was proposed to examine the early transcriptional events that occur when stem cells are stimulated with recombinant lymphokines and bone marrow stromal cell factors, using molecular biology and recombinant DNA methodology. Pluripotential hematopoietic stem cells from spleens of female NZB mice were isolated using monoclonal antibody reagents to lineage specific cell surface receptors and cell sorting by FACS. Initially, the genomic configuration and the transcriptional status of the unstimulated stem cells were determined by Southern and Northern blot analysis using cDNA probes for T cell receptors I (alpha-beta) and II(tal-delta), immnunoglobulin genes, and message for TdT transferase. The results obtained have proven, that the genome of the stem cells is still in germ-line configuration, in that rearrangement of the genes for T cell receptors or VDJ recombination for immunoglobulin mu chain gene had occurred. Further, no cytoplasmic mRNA coding for TdT transferase was detectable, indicating that even the earliest activational event such as the recruitment of template independent DNA polymerase(terminal deoxynucleotidyl transferase) had not occurred. To examine the transcriptional activity of the stimulated stem cells, Message Amplification Phenotyping (MAPping) methodology was employed. The conditions and parameters for first strand synthesis of DNA by reverse transcription and amplification by PCR using total RNA from unstimulated stem cells and oligonucleotide primers for specific genes such as beta-actin and IL-3. Experiments are in progress to identify and analyze the messages for TdT transferase, T cell receptor alpha, beta, tau, and delta chain and immunoglobulin p chain as products of the genes activated in response to stimulation of stem cells.